Severe Acute Respiratory Syndrome (SARS)

Definition: Severe acute respiratory syndrome (SARS) is a serious, potentially life-threatening viral
infection caused by a previously unrecognized virus from the Coronaviridae family, the SARS-associated
coronavirus (SARS-CoV). Since the 2002-2003 outbreak of SARS, which initially began in the
Guangdong province of southern China but eventually involved more than 8000 persons worldwide,
global efforts have virtually eradicated SARS as a threat. No further cases have been reported.
Causative agent
Severe acute respiratory syndrome (SARS) is a viral respiratory infection caused by SARS-coronavirus
(SARS-CoV).

Incubation period
Symptoms usually appear within 2 to 7 days after contracting the disease, but the incubation period can
be up to approximately 10 days.

Mode of transmission
SARS is predominantly transmitted through close person-to-person contact, via respiratory droplets
produced when an infected person coughs or sneezes. Droplet spread can take place when droplets from
the cough or sneeze of an infected person are propelled a short distance and deposited on the mucous
membranes of the mouth, nose, or eyes of persons who are nearby. The virus can also spread indirectly
when a person touches a surface or object contaminated with infectious droplets and then touches his or
her mouth, nose, or eyes.

Signs and symptoms

The clinical course of SARS generally follows a typical pattern. Stage 1 is a flulike prodrome that begins
2-7 days after incubation, lasts 3-7 days, and is characterized by the following:

 Fever (>100.4°F  Headaches  Malaise

[38°C])  Chills  Anorexia
 Fatigue  Myalgias
Less common features include the following:

 Sputum production  Coryza  Dizziness

 Sore throat  Nausea and vomiting  Diarrhea
Stage 2 is the lower respiratory tract phase and is characterized by the following:

 Dry cough
 Dyspnea
 Progressive hypoxemia in many cases
  Respiratory failure that requires mechanical ventilation in some cases

Laboratory/diagnostic tests

Researchers in several countries are working towards developing fast and accurate laboratory diagnostic
tests for the SARS coronavirus (SARS-CoV). However, until standardized reagents for virus and
antibodies detection are available and methods have been adequately field tested, SARS diagnosis
remains based on the clinical and epidemiological findings: acute febrile illness with respiratory
symptoms not attributed to another cause and a history of exposure to a suspect or probable case of SARS
or their respiratory secretions and other bodily fluids.

Those requirements are reflected in the current WHO case definitions for suspect or probable
SARS. However in several countries (Canada, France, Germany, Hong Kong SAR, Italy, Japan, the
Netherlands, Singapore, United Kingdom and the United States of America) samples from suspected and
probable SARS cases are being tested for SARS-CoV.

Laboratory test result criteria for confirming or rejecting the diagnosis of SARS remain to be
defined.
1. Molecular tests (PCR)
Polymerase chain reaction (PCR) can detect genetic material of the SARS-CoV in various specimens
(blood, stool, respiratory secretions or body tissues Sampling for Severe Acute Respiratory Syndrome
(SARS) diagnostic tests). Primers, which are the key pieces for a PCR test, have been made publicly
available by WHO network laboratories on the WHO web site. A ready-to-use PCR test kit containing
primers and positive and negative control has been developed. Testing of the kit by network members
is expected to quickly yield the data needed to assess the test’s performance, in comparison with
primers developed by other WHO network laboratories and in correlation with clinical and
epidemiological data.

Principally, existing PCR tests are very specific but lack sensitivity. This means that negative tests
cannot rule out the presence of the SARS virus in patients. Furthermore, contamination of samples in
laboratories in the absence of laboratory quality control can lead to false positive results.
Positive PCR results, with the necessary quality control procedures in place. Recommendations for
laboratories testing for SARS-coronavirus, are very specific and mean that there is genetic material
(RNA) of the SARS-CoV in the sample. This does not mean that there is live virus present, or that it is
present in a quantity large enough to infect another person.
Negative PCR results do not exclude SARS. SARS-CoV PCR can be negative for the following
reasons:
- The patient is not infected with the SARS coronavirus; the illness is due to another infectious agent
(virus, bacterium, fungus) or a non-infectious cause.
- The test results are incorrect (“false-negative”). Current tests need to be further developed to
improve sensitivity.
- Specimens were not collected at a time when the virus or its genetic material was present. The virus
and its genetic material may be present for a brief period only, depending on the type of specimen
tested.

2. Antibody tests
These tests detect antibodies produced in response to the SARS coronavirus infection. Different types
of antibodies (IgM and IgG) appear and change in level during the course of infection. They can be
undetectable at the early stage of infection. IgG usually remains detectable after resolution of the
illness.
The following test formats are being developed, but are not commercially available yet:
- ELISA (Enzyme Linked ImmunoSorbant Assay): a test detecting a mixture of IgM and IgG
antibodies in the serum of SARS patients yields positive results reliably at around day 21 after the
onset of illness.
– IFA (Immunofluorescence Assay): a test detecting IgM antibodies in serum of SARS patients yields
positive results after about day 10 of illness. This test format is also used to test for IgG. This is a
reliable test requiring the use of fixed SARS virus on an immunofluorescence microscope.
Positive antibody test results indicate a previous infection with SARS-CoV. Seroconversion from
negative to positive or a four-fold rise in antibody titre from acute to convalescent serum indicates
recent infection.
Negative antibody test results: No detection of antibody after 21 days from onset of illness seems to
indicate that no infection with SARS-CoV took place.
3. Cell culture
Virus in specimens (such as respiratory secretions, blood or stool) from SARS patients can also be
detected by inoculating cell cultures and growing the virus. Once isolated, the virus must be identified
as the SARS virus with further tests. Cell culture is a very demanding test, but currently (with the
exception of animal trials) only means to show the existence of a live virus.
Positive cell culture results indicate the presence of live SARS-CoV in the sample tested.
Negative cell culture results do not exclude SARS (see negative PCR test result).

Treatment/Management
No definitive medication protocol specific to SARS has been developed, although various treatment
regimens have been tried without proven success. The CDC recommends that patients suspected of or
confirmed as having SARS receive the same treatment that would be administered if they had any serious,
community-acquired pneumonia. The following measures may be used:

 Isolate confirmed or suspected patients and provide aggressive treatment in a hospital setting
 Mechanical ventilation and critical care treatment may be necessary during the illness.[13, 12]
 An infectious disease specialist, a pulmonary specialist, and/or a critical care specialist should
direct the medical care team
 Communication with local and state health agencies, the CDC, and World Health Organization is
critical